Deranged platelet calcium homeostasis in poorly controlled IDDM patients

OBJECTIVE - Platelet hyperfunction frequently occurs in IDDM. As in many other cellular systems, cytosolic free Ca plays a key role in platelet activation. RESEARCH DESIGN AND METHODS - We measured cytosolic free Ca concentration ([Ca2+]i) by means of the fluorescent probe fura-2 in 60 IDDM patients (mean age 30.8 yr, range 18-50 yr) and in 31 age-matched healthy control subjects. Platelets were studied in both resting conditions and after stimulation with thrombin at 0.05, 0.1, and 0.5 U/ml. RESULTS - No differences were noted between control subjects and diabetic patients, as a whole. Patients with a poor metabolic control (HbA1c >8%) had significantly (P < 0.01 and P < 0.03) higher [Ca2+]i in resting platelets. The presence or absence of retinopathy did not modify resting platelet [Ca2+]i. After stimulation with thrombin, a significantly (P < 0.009) higher rise of platelet [Ca2+]i was observed only in those patients who were both free from complications and had good metabolic control. A highly significant (P < 0.001) correlation was found between resting [Ca2+]i and both blood cholesterol and HbA1c in the diabetic patients. Platelets from 10 young healthy subjects also were studied after in vitro incubation with various glucose concentrations (from 1.68 to 56 mM): resting and thrombin-stimulated platelet [Ca2+]i and thrombin-induced aggregation were not modified. CONCLUSIONS - These data confirm that platelet hyperfunction is present in IDDM patients who have unsatisfactory metabolic control, and give evidence that such an activation involves Ca homeostasis. Acute variations of blood glucose concentration are probably not influent, in this respect.